While the effects of visual deprivation have been well studied in animal models, much less is known about the effects of blindness on human early visual pathways. Understanding the effects of visual deprivation on early visual pathways in humans is important for two reasons. First, a deeper understanding of the effects of blindness will prove increasingly important as new sight restoration procedures (such as retinal prosthetic implants, epithelial stem cell replacements, gene therapies and retinal transplants) become available over the next few decades. Second, blindness due to peripheral causes is an excellent model system for understanding prenatal, postnatal and adult cortical plasticity. We propose to use a combination of "state-of-the-art" MR imaging techniques to examine the effects of blindness on human sub-cortical and cortical visual pathways. Four subject groups will be compared: anophthalmic (born without eyes), non-anophthalmic congenitally blind, late blind and normally sighted control subjects. High resolution structural imaging will be used to measure changes in the size of the lateral geniculate nucleus and changes in the size and myelination patterns of area V1 as a consequence of early blindness. Probabilistic tractography will be used to measure the effects of early blindness on connections between the lateral geniculate nucleus and V1, and between V1 and the corpus callosum. Magnetic resonance spectroscopy will be used to examine the neurochemical effects of blindness on myelination processes and metabolic, cholinergic, and GABA-ergic pathways within blind individuals. Our inclusion of anophthalmic, early blind and late blind subjects will allow us to compare the effects of embryonic development, postnatal development, and adult visual deprivation on sub-cortical and cortical development in humans. This work is likely to have significance not only for understanding development of the human visual system, but also for understanding large-scale developmental sub-cortical and cortical plasticity in general. PUBLIC HEALTH RELEVANCE: While the effects of visual deprivation have been well studied in animal models, much less is known about the effects of blindness on human early visual pathways. We propose to use a combination of "state-of-the-art" MR imaging techniques (high resolution structural imaging, probabilistic diffusion tractography, and magnetic resonance spectroscopy) to examine the effects of blindness on early stages of visual processing. This work is likely to have significance not only for our understanding of the development of the human visual system, but also for improving our general understanding of large scale sub-cortical and cortical plasticity.